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991.
Kondo F 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》2000,120(2):159-169
Microcystins, produced by freshwater cyanobacteria, are cyclic peptide hepatotoxins and tumor promoters. An outbreak of human poisoning attributed to microcystins has been reported in Caruaru, Brazil in 1996, where exposure through renal dialysis led to the death of 50 patients. Although such severe acute effects on human health seem to be rare, microcystins poses problems to human health which could result from low-level, chronic exposure to microcystins in drinking water. It is therefore important to monitor the levels of microcystins in water reservoirs where cyanobacterial blooms occur. We have developed a total analysis system for microcystins using GC-MS and LC-MS. This comprises initial screening of samples to check for the presence of microcystins by detecting 2-methyl-3-methoxy-4-phenylbutyric acid as an ozonolysis product using thermospray interface LC-MS and electron ionization/GC-MS. If a sample is positive in a screening test, it will be necessary to follow through with identification and quantification. Frit-FAB interface LC-MS allowed the rapid identification of microcystins in cyanobacteria and lake water, and also enabled us to identify microcystins and their metabolites formed in vivo in mouse liver. Finally, Frit-FAB/LC-MS using selected ion monitoring could be used for quantitative analysis of microcystins in lake water in the low nanogram range. The total analysis system proposed in the present study should be applicable to studies of the metabolism of microcystins, of their detoxification, and those of the mechanism(s) of the accumulation in the food chain. 相似文献
992.
Sakuda S Ikeda H Nakamura T Kawachi R Kondo T Ono M Sakurada M Inagaki H Ito R Nagasawa H 《The Journal of antibiotics》2000,53(12):1378-1384
Blasticidin A (1), an antibiotic, has strong inhibitory activity toward aflatoxin production by Aspergillus parasiticus. We prepared some derivatives of 1 and examined their biological activities. Among them, derivatives 3 and 4 without the tetramic acid moiety of 1 maintained inhibitory activity toward aflatoxin production, but did not show antifungal activity or toxicity. RT-PCR experiments indicated that derivatives 3 and 4 as well as 1 significantly reduced the expression of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1 and omtA) and a regulatory gene (aflR) in A. parasiticus. These results suggested that derivatives 3 and 4 can inhibit aflatoxin production more specifically than 1 by inhibiting an early step prior to the expression of aflR in the pathway of aflatoxin biosynthesis. 相似文献
993.
994.
995.
Xiao-Jin Li Dong-Yu Wang Yue Zhu Rong-Jun Guo Xing-Duo Wang Kaco Lubomir Kiyoshi Mukai Hiroki Sasaki Haruhiko Yoshida Teruaki Oka Rikuo Machinami Kazuya Shinmura Masamitsu Tanaka Haruhiko Sugimura 《Cancer science》1999,90(7):740-746
Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor celllines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma. 相似文献
996.
Kimura T Miki M Watanabe K Kondo S Ho IK Yamamoto I 《Xenobiotica; the fate of foreign compounds in biological systems》2000,30(6):643-653
1. The metabolism of N3-phenacyluridine (3-phenacyl-1-beta-D-ribofuranosyluracil), a potent hypnotic nucleoside derivative, was studied in mouse. 2. Of the radioactivity, 65% was excreted in urine within 48 h after intraperitoneal (i.p.) administration of [3H]N3-phenacyluridine. The urinary metabolites N3-phenacyluracil and N3-alpha-hydroxy-beta-phenethyluridine were extracted, isolated and analyzed by mass spectrometry. 3. Racemates of N3-alpha-hydroxy-beta-phenethyluridine were synthesized and both isomers were separated as N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine by hplc (CHIRALCEL-OJ column) with retentions of 13.8 and 17.9 min respectively. The reduction process took place with high stereo-selectivity, which gave an alcohol product in the urine with the same retention (17.9 min) as one of the synthetic isomers separated by hplc. 4. One of urinary metabolites was identified as N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. N3-phenacyluridine was predominantly converted to an alcoholic metabolite of (S)-(+)-configuration. 5. N3-phenacyluracil and uridine were also identified as minor metabolites. 6. The pharmacological effects of the metabolites and related compounds were also evaluated in mouse. N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, possessed hypnotic activity and potentiated pentobarbital-induced sleeping time with a similar potency to the parent compound, N3-phenacyluridine. N3-alpha-hydroxy-beta-phenethyluridine (racemate) had almost two thirds of the hypnotic activity of N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. No other metabolites exhibited hypnotic activities. 7. The present study indicates that N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, a major metabolite of N3-phenacyluridine, is an active metabolite and contributes a significant CNS depressant effect. 相似文献
997.
Nishikawa T Kamijo Y Kondo R Sugie H Kurihara K Okuda T Matsumoto N Okada Y Ohtani H 《Journal of analytical toxicology》2000,24(8):691-695
Bromoisovalerylurea (bromisovalum) is a sedative-hypnotic given orally as a racemic mixture of optical isomers (i.e., (+)- and (-)-enantiomer) and frequently taken in overdose in order to commit suicide. Sera from 16 overdosed subjects were analyzed for each enantiomer by high-performance liquid chromatography on chiral stationary phases. The (+)-enantiomer concentration was lower than the (-)-enantiomer concentration in all specimens, that is, the ratio of the (+)-enantiomer to the total concentration ranged from about 50% to 0%. The ratio of the (+)-enantiomer was continuously decreasing in each subject. The data indicate that the drug in gastrointestinal tract was absorbed into blood nonstereoselectively and that the drug in blood was eliminated stereoselectively. The enantioselective determination of this drug will give useful information on absorption and elimination. 相似文献
998.
Matsuda K Shimomura M Kondo Y Ihara M Hashigami K Yoshida N Raymond V Mongan NP Freeman JC Komai K Sattelle DB 《British journal of pharmacology》2000,130(5):981-986
1. The nitroguanidine insecticide imidacloprid along with a second generation of related compounds including nitenpyram, all nicotinic acetylcholine (ACh) receptor ligands, are used increasingly in many countries. Site-directed mutagenesis and heterologous expression in XENOPUS: laevis oocytes have been deployed to investigate mutants (G189D and G189E) of the chicken alpha7 homomer-forming nicotinic receptor subunit which are predicted to enhance the negative charge at the negative subsite (loop D) of the ACh binding site. 2. XENOPUS: oocytes expressing wild-type alpha7 nicotinic receptors respond to imidacloprid with rapid inward currents. Imidacloprid and nitenpyram are partial agonists, whereas ACh, (-)-nicotine and (+)-epibatidine are full agonists. 3. Compared to wild-type alpha7, the mutant G189D and G189E receptors are much less sensitive to the insecticides, whereas their sensitivity to (-)-nicotine, ACh and (+)-epibatidine is only slightly reduced. In contrast, G189N and G189Q mutants are sensitive not only to ACh, (-)-nicotine and (+)-epibatidine, but also to the two insecticides. Thus reduction of the insecticide-sensitivity by the mutations G189D and G189E are attributed to an increase in negativity of loop D. Desnitro-imidacloprid (DN-IMI), an imidacloprid derivative lacking the nitro group is a potent agonist on the G189D and G189E mutants suggesting an important role of loop D in nicotinic receptor interactions with the nitro group of nitroguanidine insecticides. 相似文献
999.
Masumi Sawada Yoshiaki Matsui Kenichi Hayakawa Haruhiko Nishiura Yoshio Okudaira Ichiro Taki 《Gynecologic oncology》1982,13(2):220-228
The serial transplants of human ovarian and endometrial tumors in nude mice were transplanted into nude rats. The transplants consisted of three lines of yolk sac tumors, designated as YST-1, YST-2, and YST-3 and two lines of endometrial adenocarcinoma, AD-30 and AD-35. The transplanted tumors grew much larger in nude rats than in nude mice, reaching more than 150 g in weight. The overall grafting success rate of these tumors was about 70% in nude rats whereas it had been almost 100% in nude mice. The histology of the transplanted tumor in nude rats was similar to that of the same tumor in nude mice. YST-1, YST-2, and YST-3 tumors produced the marker α-fetoprotein (AFP). Thus the transplanted tumors in nude rats seemed to preserve the characteristics of the original tumors. The usefulness of the nude rat as a tool for studying the efficacy of treatments on human malignant tumors is discussed. 相似文献
1000.
OBJECTIVE To determine the usefulness of vectorcardiography (VCG) in assessing myocardial infarct size.
METHODS The correlation of spatial and scalar parameters of VCG with the percent defect volume (%DV) of thallium myocardial single photon emission computed tomography (SPECT) was investigated in 63 patients with first-onset myocardial infarction (MI). VCG parameters included: (1) spatial parameters: magnitude, azimuth and elevation of the maximal vector, vectors at 20 ms and 30 ms, and (2) scalar parameters: amplitudes of 20 ms and 30 ms vectors at X, Y, and Z scalar leads abbreviated as X20, Y20, Z20, X30, Y30 and Z30, respectively.
RESULTS For anteroseptal MI, the azimuth of 30 ms vector and Z20 showed a significant correlation with %DV (r = 0.572, P < 0.05 and r = 0.832, P < 0.001) while in anteroseptal MI with involvement of lateral wall, the azimuth of 30 ms vector and X30 were correlated with %DV significantly (r = 0.775, and r = 0.780, P < 0.01). For inferior and inferoposterior MI, the elevation of 30 ms vector and Y30 were correlated well with %DV (r = 0.871, P < 0.01, r = 0.928, P < 0.001 for inferior MI and r = 0.678, P < 0.01, r = 0.760, P < 0.001 for inferoposterior MI).
CONCLUSIONS VCG parameters, especially scalar parameters, can be used to evaluate myocardial infarct size easily and non-invasively with remarkable accuracy.
相似文献